PMID- 26441517
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151007
LR  - 20230714
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 8
DP  - 2015
TI  - NF-kappaB mediates Gadd45beta expression and DNA demethylation in the hippocampus during 
      fear memory formation.
PG  - 54
LID - 10.3389/fnmol.2015.00054 [doi]
LID - 54
AB  - Gadd45-mediated DNA demethylation mechanisms have been implicated in the process 
      of memory formation. However, the transcriptional mechanisms involved in the 
      regulation of Gadd45 gene expression during memory formation remain unexplored. 
      NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) controls 
      transcription of genes in neurons and is a critical regulator of synaptic 
      plasticity and memory formation. In silico analysis revealed several NF-kappaB 
      (p65/RelA and cRel) consensus sequences within the Gadd45beta gene promoter. Whether 
      NF-kappaB activity regulates Gadd45 expression and associated DNA demethylation in 
      neurons during memory formation is unknown. Here, we found that learning in a 
      fear conditioning paradigm increased Gadd45beta gene expression and 
      brain-derivedneurotrophic factor (BDNF) DNA demethylation in area CA1 of the 
      hippocampus, both of which were prevented with pharmacological inhibition of 
      NF-kappaB activity. Further experiments found that conditional mutations in p65/RelA 
      impaired fear memory formation but did not alter changes in Gadd45beta expression. 
      The learning-induced increases in Gadd45beta mRNA levels, Gadd45beta binding at the 
      BDNF gene and BDNF DNA demethylation were blocked in area CA1 of the c-rel 
      knockout mice. Additionally, local siRNA-mediated knockdown of c-rel in area CA1 
      prevented fear conditioning-induced increases in Gadd45beta expression and BDNF DNA 
      demethylation, suggesting that c-Rel containing NF-kappaB transcription factor 
      complex is responsible for Gadd45beta regulation during memory formation. Together, 
      these results support a novel transcriptional role for NF-kappaB in regulation of 
      Gadd45beta expression and DNA demethylation in hippocampal neurons during fear 
      memory.
FAU - Jarome, Timothy J
AU  - Jarome TJ
AD  - Department of Neurobiology, University of Alabama at Birmingham Birmingham, AL, 
      USA.
FAU - Butler, Anderson A
AU  - Butler AA
AD  - Department of Neurobiology, University of Alabama at Birmingham Birmingham, AL, 
      USA.
FAU - Nichols, Jessica N
AU  - Nichols JN
AD  - Department of Neurobiology, University of Alabama at Birmingham Birmingham, AL, 
      USA.
FAU - Pacheco, Natasha L
AU  - Pacheco NL
AD  - Department of Neurobiology, University of Alabama at Birmingham Birmingham, AL, 
      USA.
FAU - Lubin, Farah D
AU  - Lubin FD
AD  - Department of Neurobiology, University of Alabama at Birmingham Birmingham, AL, 
      USA.
LA  - eng
GR  - K99 MH082106/MH/NIMH NIH HHS/United States
GR  - T32 NS061788/NS/NINDS NIH HHS/United States
GR  - R56 MH097909/MH/NIMH NIH HHS/United States
GR  - R01 MH097909/MH/NIMH NIH HHS/United States
GR  - R00 MH082106/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20150916
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC4584956
OTO - NOTNLM
OT  - DNA demethylation
OT  - Gadd45
OT  - hippocampus
OT  - memory
OT  - nuclear factor kappa B
EDAT- 2015/10/07 06:00
MHDA- 2015/10/07 06:01
PMCR- 2015/01/01
CRDT- 2015/10/07 06:00
PHST- 2015/07/06 00:00 [received]
PHST- 2015/08/30 00:00 [accepted]
PHST- 2015/10/07 06:00 [entrez]
PHST- 2015/10/07 06:00 [pubmed]
PHST- 2015/10/07 06:01 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2015.00054 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2015 Sep 16;8:54. doi: 10.3389/fnmol.2015.00054. eCollection 
      2015.